Archives of pathology & laboratory medicine最新文献

Context.—: Drug-induced autoimmune-like hepatitis (DI-ALH) and idiopathic autoimmune hepatitis (iAIH) share similar clinical, biochemical, serologic, and histologic features. Differentiating between them is crucial for treatment and prognosis.

Objective.—: To identify clinical and histologic factors that distinguish DI-ALH from iAIH and develop a predictive scoring algorithm.

Design.—: We evaluated diagnostic laboratory data and histologic features from index liver biopsies of 14 well-characterized DI-ALH cases and compared them with those from 19 age- and sex-matched iAIH cases. Data included age, sex, autoantibodies (anti-nuclear antibody, anti-smooth muscle antibody), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase, immunoglobulin G, and total bilirubin (T. Bili). Histologic evaluation included modified Ishak scores, histologic activity index (HAI), type of portal inflammation, zonality of lobular inflammation, plasma cell clusters, cholestasis, bile duct damage, ballooning degeneration, portal endothelialitis, central venulitis, ceroid macrophages, lobular disarray, polyglucosan inclusions, bile duct loss, and ductular reaction. Fibrosis was assessed by using the Scheuer and Ishak systems.

Results.—: A scoring algorithm with weighted scores for ALT above 289.5 U/L, AST above 303.5 U/L, ALP above 119.5 U/L, T. Bili above 0.65 mg/dL, HAI above 9.5, zone 2 sparing, lobular disarray, ballooning degeneration, ceroid macrophages, central venulitis, and advanced Ishak fibrosis yielded a receiver operating characteristic area under the curve of 0.99, with an optimal cutoff score of 6.5 favoring DI-ALH.

Conclusions.—: A scoring algorithm that incorporates specific liver biopsy findings, HAI, and liver biochemistry profiles effectively distinguishes DI-ALH from iAIH.

Context.—: In silico mutagenesis can be performed to introduce variants into next-generation sequencing data. This method holds potential promise for proficiency testing since rare or novel variants can be modeled that are not found in available proficiency testing materials.

Objective.—: To determine whether in silico mutagenesis could be used as a viable proficiency testing methodology for undiagnosed disorders by exome sequencing.

Design.—: Laboratories performed exome sequencing on reference samples and uploaded raw sequence data files to the College of American Pathologists. These files were then mutagenized in silico to introduce variants, including those deemed to be causative for the clinical scenario provided. The laboratories processed the mutagenized files through their bioinformatic pipelines and performed interpretation to identify pathogenic and likely pathogenic primary and secondary findings. Responses were evaluated for concordance with intended responses.

Results.—: A total of 7 educational (nongraded) proficiency testing challenges were performed between 2018 and 2021. An average of 47 laboratories participated in each program, which each containing between 2 to 5 (average = 3.6) intended response variants. Intended response variant types included substitutions and small insertion/deletion variants. Participating laboratories returned 94.3% of intended response variants across all programs on average (per program range, 91.5%-97.3%). The percentage of laboratories that correctly returned all intended response variants for a program ranged from 70.0% to 96.7%.

Conclusions.—: In silico mutagenesis represents a suitable approach for graded intended response-based proficiency testing for exome sequencing that allows laboratories to assess both analytical and interpretative components of the test.

Context.—: Pathology is essential to global health care, yet disparities remain in access to education and training. The College of American Pathologists (CAP) Foundation addresses these gaps through grants and awards that support trainees, early-career pathologists, and initiatives promoting equity worldwide. Since 2015, total funding has increased from $18,400 to $84,098, an astounding 357%.

Objective.—: To evaluate the CAP Foundation Grants and Awards Program during a 10-year period, assessing financial investment, award distribution, recipient characteristics, and impact.

Design.—: A mixed-methods retrospective study integrated (1) quantitative analysis of program data, (2) qualitative feedback from awardees, and (3) a quantitative award impact survey of past CAP Foundation awardees. Variables included demographics, award type, funding amounts, geographic distribution, and career stage. Surveys assessed professional development, mentorship, and long-term engagement with CAP.

Results.—: From 2015 to 2024, a total of 744 applicants submitted 760 applications, resulting in 355 awards across 14 categories. Applications increased more than 8-fold, peaking in 2023, with surges during the COVID-19 pandemic. Medical student applications grew from 1 in 2020 to 17 in 2024 (76% annual growth); 9 of 12 Medical Student Travel Award recipients (75%) entered pathology residency. Geographic disparities were noted, with smaller residency programs showing higher per capita application rates. Among 174 survey respondents, 129 (74%) reported networking benefits, 127 (73%) learning benefits, and 99 (57%) mentorship benefits, though only 49 (28%) sustained long-term mentoring relationships.

Conclusions.—: The CAP Foundation's awards program has expanded access, supported career development, and fostered future pathologists. Strengthening long-term mentorship and bridging education-to-practice gaps may further enhance its impact.

Context.—: Pancreatobiliary maljunction (PBM) is a congenital malformation characterized by the pancreatic and common bile ducts joining anatomically outside the duodenal wall, resulting in the formation of a long common channel. PBM-associated conditions include choledochal cysts and reflux-associated cholecystopathy. Precursor lesions, such as biliary intraepithelial neoplasias, intraductal papillary neoplasms of the bile duct, intracholecystic papillary neoplasms, and cancers associated with PBM, occur in the gallbladder, bile duct, and pancreas. Most PBM cases, along with their associated conditions, precursor lesions, and cancers, have been reported in Asian countries, including Japan and South Korea. However, recent studies have shown no significant difference in frequency between Eastern and Western populations.

Objective.—: To summarize the current understanding of PBMs, as well as recent developments related to associated precursor lesions and cancers.

Data sources.—: To understand the clinicopathologic characteristics of PBMs and their associated precursor lesions and cancers, reports from PubMed (US National Library of Medicine) were reviewed.

Conclusions.—: PBM is a congenital malformation diagnosed primarily by gastroenterologists and radiologists. Pathologists diagnose PBM-associated conditions, including choledochal cysts and reflux-associated cholecystopathy. PBM-related precursor lesions and cancers can develop in the gallbladder, bile duct, and pancreas. Therefore, understanding PBM-associated conditions is crucial for the early detection and effective treatment of patients with PBM-related cancers.

Context.—: Distinguishing benign from malignant processes in small lung biopsy specimens is challenging, particularly in the presence of architectural distortion and crush artifacts. Mimics include reactive type II pneumocytes in peribronchiolar metaplasia or organizing pneumonia and benign mucinous elements, including goblet cells and submucosal glands, which can mimic adenocarcinoma with mucinous features.

Objective.—: To understand whether caudal-type homeobox 2 (CDX2) and cytokeratin 20 (CK20) immunoreactivity is specific to malignant epithelial processes and evaluate their expression in a range of benign, premalignant, and malignant pulmonary lesions.

Design.—: We assessed CDX2 and CK20 immunohistochemistry in 48 cases of interstitial lung disease with reactive type II pneumocytes, 13 foci of atypical adenomatous hyperplasia, 11 bronchiolar adenomas, 4 adenocarcinomas in situ, 25 minimally invasive adenocarcinomas, 39 pulmonary adenocarcinomas with mucinous features, 6 mucoepidermoid carcinomas, and 1 squamous papilloma with goblet cell hyperplasia.

Results.—: No expression of CDX2 or CK20 was observed in reactive processes, goblet cells, bronchial glands, atypical adenomatous hyperplasia, or bronchiolar adenomas. In adenocarcinomas with mucinous features (n = 39), 9 (23%) were CK20-reactive and 8 (20%) were CDX2-reactive. A minority of nonmucinous and mucinous minimally invasive adenocarcinomas (n = 25) showed immunoreactivity (3 [12%] for each marker), while all in situ adenocarcinomas were negative.

Conclusions.—: Our findings demonstrate that CDX2 and CK20 are not expressed in benign or reactive type II pneumocytes and are specific for malignancy, particularly adenocarcinomas with mucinous features. Immunoreactivity with either marker in small biopsy specimens can support a diagnosis of malignancy, especially in morphologically equivocal or limited samples. Absence of staining does not exclude malignancy, but immunoreactivity with CDX2 and/or CK20 provides strong supportive evidence for a malignant process.

Context.—: In April 1946, Archives of Pathology published H. G. Schlumberger's seminal study on anterior mediastinal (AM) teratomas that provided insights into the clinical behavior, pathologic features, and pathogenesis of these enigmatic neoplasms.

Objective.—: To review key points of Schlumberger's study, add more recent information, discuss the different types of mediastinal teratoma and germ cell tumors (GCTs), and consider the origin of the neoplasms.

Data sources.—: Schlumberger's article, PubMed-indexed articles on the topic, and personal observations.

Conclusions.—: Pure teratomas of the AM in children are benign type I GCTs that may dedifferentiate to yolk sac tumor, possibly from embryonic-type neuroectoderm. Mature teratomas in postpubertal patients, comprising ∼95% of GCTs in females but only ∼30% in males, are hybrid type I and type IV teratomas. Such cases show organoid structures and benign cytology. They derive from nontransformed germ cells and lack metastatic potential. Immaturity does not alter the outcome in children. In contrast, many teratomas in postpubertal males are type II GCTs, derived from malignantly transformed germ cells that initially form a primitive GCT, with subsequent teratomatous differentiation. These teratomas, consequently, are components of mixed GCTs and show cytogenetic abnormalities, including overrepresentation of chromosome arm 12p. They are cytologically atypical and less commonly organoid; their most frequent associated GCT is yolk sac tumor, which may be the source of somatic-type malignancies of type II AM GCTs, especially the virtually uniquely associated hematologic malignancies and vascular neoplasms of GCT origin. All AM GCTs are believed to derive from mismigrated germ cells.

Context.—: Thyroid gland neoplasia comprises the most common group of tumors arising within organs of the endocrine system. Pathogenic molecular changes can now be identified in up to 90% of thyroid carcinomas. These alterations not only shape our understanding of tumor biology and classification, but also increasingly guide therapeutic approaches to these diseases.

Objective.—: To revisit a frequently cited review article from 2011 that outlined fundamental differences between tumor types-primarily papillary thyroid carcinoma and follicular neoplasia-in terms of their underlying genetic profiles. The present review discusses the aspects of the preceding manuscript that have remained salient, as well as advances in thyroid molecular pathology that have transpired in the intervening years.

Data sources.—: Primary literature and review articles were evaluated in order to consider topics addressed in the original review, and to gauge progress that has occurred since its publication.

Conclusions.—: The distinction between the respective molecular signatures of papillary thyroid carcinoma and follicular neoplasia, and the specter of alterations associated with aggressive cancers, remain pertinent in the present era. Important changes since 2011 relate to the reorganization of diagnostic categories, the prospect of molecular alterations in (or their incompatibility with) nonneoplastic processes, and the variety of available molecular testing platforms. Molecular analysis of thyroid nodules now factors into every step along the gamut from initial assessment to definitive classification to subsequent guidance of management. Nikiforov's review established a conceptual framework around thyroid neoplasia that has evolved over time, but endures as the dominant paradigm regarding these tumors.

Context.—: Nearly a century has passed since a seminal review article was published in 1928 in Archives of Pathology on ectopic endometriosis, presenting the dominant pathogenetic theories of the era: the serosal theory suggesting that endometriosis would arise by metaplasia of the peritoneal mesothelium; the metastatic theory implying the role of uterine lymphovascular invasion by endometrial tissue; and the implantation theory. Since then endometriosis has been the subject of numerous studies due to the associated morbidity and its significant impact on patients' quality of life and health care costs.

Objective.—: To provide an overview of our evolving understanding of pathogenesis and clinicopathologic features of endometriosis.

Data sources.—: Review of the literature and personal experience of the authors.

Conclusions.—: The prevailing pathogenetic theory of endometriosis remains the retrograde menstruation and implantation theory proposed by Sampson in the 1920s. Contemporary studies have focused on the additional role of inherited genetic components, a supportive microenvironment, and molecular genetic alterations to improve the clinical classification, prognostication, and therapeutic options for patients with endometriosis.